It is known that radiosensitive lymphocytes which arise in the reticular tissue of the lymph glands are the cells primarily responsible for the recognition and destruction of allografts. It follows, therefore, that lymphoid ablation should inhibit or prevent the rejection of allografts.
In the past total body irradiation (TBI) utilizing an external beam has been utilized to abrogate allograft rejection. However, the dose of TBI required for a permanent acceptance of an allograft is lethal to bone marrow cells, both proximal and distal, and to the cells of the gastro-intestinal mucosa. This and other complications have led the art to seek immunosuppresive methods employing radioactive compounds, the .beta.-emissions of which will selectively destroy lymphoid tissue.
It is known that .sup.109 Pd labeled hematoporphyrin, a .beta.-emitting radioactive agent with a half life of 13.4 hours, a beta emission of 1.028 MeV maximum, and a scatter area of 2 mm can satisfy many of the criteria for this purpose. (Fawwaz et al, J. Nucl. Med. 12:231-236, 1981 and Fawwaz et al, J. Nucl. Med. 15:997-1002, 1974) Palladium-109-hematoporphyrin (Pd-H) preferentially localizes in lymphoid organs as well as in the liver, kidney and central bone marrow. The affinity of Pd-H for distal bone marrow and intestinal tissue is low. In the rat a single treatment of a future transplant recipient with sublethal Pd-H (24 m Ci/Kg) and rabbit anti-rat lymphocyte globulin (ALG) leads to permanent cardiac allograft acceptance across a minor histocompatibility barrier and a significant prolongation across a major histocompatibility difference.
Unfortunately, Pd-H has a relatively high concentration in non-lymphoid organs such as the liver, kidney, adrenals and ovaries. For this reason the art has continued to seek other .beta.-emitters which will concentrate more selectively in the lymphoid organs, thereby to inhibit the rejection of allografts by lymphoid ablation.